Surgical method and composition utilizing submucosal tissue to prevent incisional hernias

ABSTRACT

A small intestine submucosa mesh is adapted for use in surgical abdominal closure routines. The submucosa mesh is incorporated into the normal surgical protocol for abdominal closure procedures. The submucosa mesh is applied to the abdominal incision area and maintains and enhances the stability and integrity of the abdominal wall closure, thereby preventing the onset or occurrence of incisional hernias. The submucosa mesh can also be applied to surgical closure procedures involving treatment of a hernia defect, such as an incisional hernia or other non-incisional hernia. The submucosa construct can also be adapted for use as a suturing component or bioretention suture. The submucosa construct can be adapted for use as part of a surgical strategy to facilitate wound healing, regeneration, reconstruction, and replacement of anatomical structures, such as tissues and organs.

This application hereby claims the benefit under Title 35, United StatesCodes § 119 (e) of any U.S. application Ser. No. 60/472,797 filed May21, 2003, and is hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to surgical procedures andcompositions suitable for use in surgical applications, and, moreparticularly, to the formation of a tissue graft construct employing asmall intestine submucosa mesh and its use in various surgicalprotocols, such as abdominal closure incisions, hernia defect repair,and internal bioretention sutures.

2. Description of the Related Art

Medical procedures involving peritoneal access into the abdominal wallcavity typically need to address the incidence of incisional hernias asone possible future complication. It is known that 7% of patients havingabdominal incisions will develop incisional hernias. This percentageincreases with smoking, obesity, wound infections, malnourishedpatients, diabetes, and other known conditions.

A need exists to develop a surgical technology that mitigates theincidence of post-operative incisional hernias, which is cost effective,readily amenable to use in routine abdominal closure regimens, and doesnot necessitate any additional surgical procedures beyond what isalready warranted by the abdominal closure specification.

Additionally, current retention sutures, such as those typicallyemployed to facilitate an abdominal closure or otherwise treat anincision, are very painful to the patient since they are external andtend to pull on the abdominal wall. The conventional sutures also tendto dig into the skin, causing irritation, infection and unsightly scars.

A need therefore exists to develop a suturing technology that overcomesthese problems.

SUMMARY OF THE INVENTION

According to the present invention, there is provided a small intestinesubmucosa mesh adapted for use in surgical abdominal closure routines.In particular, application of the submucosa mesh is incorporated intothe surgical protocol for conventional abdominal closure procedures.This application of the submucosa mesh is especially adapted as apreventative measure to maintain, enhance, improve, and fortify thestability and integrity of the abdominal wall closure and therebyprevent the onset or occurrence of incisional hernias. The submucosamesh provides particular long-term strength to the fascial closure.

In another form, the submucosa mesh can be applied to surgical closureprocedures involving treatment of a hernia defect, such as an incisionalhernia or other non-incisional hernia.

In another form, the submucosa construct can be adapted for use as asuturing component. In one exemplary configuration, the submucosa sutureis arranged as a bioretention suture.

In another form, a submucosa construct is developed that can be used aspart of a surgical strategy to facilitate wound healing, regeneration,reconstruction, and replacement of anatomical structures, such astissues and organs.

One advantage of the present invention is that the submucosa meshconstruct is readily adapted and amenable for direct use in the standardabdominal wall closure and/or suturing protocols found in conventionalsurgical procedures.

Another advantage of the present invention is that the use of thesubmucosa mesh construct in abdominal wall closure procedures provides asignificant deterrent to the subsequent onset and occurrence ofincisional hernias.

A further advantage of the invention is that the submucosa meshconstruct can be readily adapted for use in surgical proceduresaddressing the treatment of hernia defects.

Another advantage of the invention is that the submucosa articleconstruct can be adapted for use as an effective implantable internalsuture to thereby eliminate the conventional requirement of externalsutures.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned and other features and advantages of this invention,and the manner of attaining them, will become more apparent and theinvention will be better understood by reference to the followingdescription of an embodiment of the invention taken in conjunction withthe accompanying drawings, wherein:

FIG. 1 is a planar diagrammatic view of a submucosa mesh, according toone form of the invention;

FIG. 2 is a planar diagrammatic view illustrating the use of thesubmucosa mesh of FIG. 1 in an incisional abdominal closure applicationto prevent incisional hernias, according to another form of theinvention;

FIG. 3 is a planar diagrammatic view illustrating the use of thesubmucosa mesh of FIG. 1 in an abdominal closure application to repair ahernia defect, according to another form of the invention;

FIG. 4 is a planar diagrammatic view illustrating the use of submucosapatch elements as suturing components, according to another form of theinvention; and

FIG. 5 is a planar diagrammatic view illustrating a combinationincluding the submucosa mesh of FIG. 1 and the submucosa patch elementsof FIG. 4 for use in a surgical application, according to another formof the invention.

Corresponding reference characters indicate corresponding partsthroughout the several views. The exemplification set out hereinillustrates one preferred embodiment of the invention, in one form, andsuch exemplification is not to be construed as limiting the scope of theinvention in any manner.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the drawings and particularly to FIG. 1, there is shownin illustrative depiction a submucosal mesh 10 that constitutes, invarious alternate forms, a tissue graft composition, material, articleand/or construct, according to one form of the invention. Reference isalso made to FIG. 2, which illustrates the use of mesh 10 in a surgicalprocedure, namely, an abdominal closure routine, according to anotherform of the invention.

Referring to FIG. 1, submucosa mesh 10 is formed by any suitable meansknown to those skilled in the art. For example, mesh 10 will possessproperties upon fabrication that enable it to be biocompatible with aninternal human environment, namely, suitable for permanent implantationand use at internal sites of the body.

The geometry of mesh 10 will be tailored to the intended application andsurgical environment. Accordingly, although mesh 10 is shown in agenerally rectangular form, this depiction is for illustrative purposesonly and should not be considered in limitation of the invention, as itshould be apparent to those skilled in the art that any other suitablesize, shape and form can be used depending upon the specifications ofthe surgical routine. Mesh 10, in alternate forms, can be considered asolid body tissue structure (e.g., three- dimensional) having adimensional profile suited to the intended application. For example, insome applications, it may be desirable to provide mesh 10 as arelatively thin sheath-type construct formed as a planar-type tissuesheet. It may also be desirable to provide mesh 10 in a relatively smallform such as a patch-type construction to facilitate multiple placementsof mesh 10 at various targeted sites, e.g., several incision sites.

Alternately, for uses such as reconstruction or replacement of an organor other anatomical or physiological entity or structure, it may benecessary to provide mesh 10 in a form that resembles or models thetargeted anatomical entity in a template-type manner. For example, mesh10 can be constituted as a substrate or host structure that replaces, inwhole or in part, the target body part. For this purpose, mesh 10 willbe suitably formed in a manner known to those skilled in the art thatenables mesh 10 upon implantation to readily assimilate, incorporate,and otherwise integrate into the internal environment. Additionally, ina reconstruction or replacement applications, mesh 10 will be fashionedto substantially duplicate as much as practicable the functional andstructural aspects of the replaced body part. In essence, mesh 10 willserve as an effective functional equivalent of the replaced target bodypart.

Mesh 10 can also be constituted as a multi-piece construction that isformed, for example, from multiple submucosa tissue sheets integratedtogether to form a cohesive multi-layered, multi-laminate ormulti-tiered construct.

It should be apparent that mesh 10 can be readily conditioned, treatedand/or processed to make it suitable for use at internal body sites,according to conventional means known to those skilled in the art.Furthermore, mesh 10 will be formed to possess chemical, biological,mechanical, and/or physiological properties and characteristics thatpromote its integrity, durability, and functionality upon itsimplantation or placement in the body.

In one alternate form, mesh 10 can be constituted as a small intestinesubmucosa (SIS) construct. For example, the SIS construct can be formedfrom submucosa of a warm-blooded vertebrate, wherein the submucosa isdelaminated from both the external smooth muscle layers and the luminalportions of the tunica mucosa. In one form, the submucosa comprisestunica submucosa delaminated from both the tunica muscularis and atleast the luminal portion of the tunica mucosa of vertebrate intestinaltissue.

In various forms, depending upon the application, the SIS constructsdiscussed herein can be considered to constitute, without limitation,artificial organ or tissue constructs; prosthetic structures;implantable articles; incisional closure mechanisms; suturingmechanisms; and/or a remodeling template for the ingrowth of patientcells.

The functional uses of the SIS constructs discussed herein can beconsidered to include, but is not limited to, the prevention ofincisional hernias; the repair of hernia defects; general suturing; therepair, replacement or reconstruction of damaged or diseased ornon-functioning tissues, organs, or physiological units or parts; thetreatment of patients with diseased or damaged organs or tissues; tissueor organ augmentation; promoting endogenous regrowth and healing ofdamaged or diseased tissues; and/or tissue or organ substitution.

Among its various aspects, the submucosa constructs discussed herein mayexhibit material and functional properties including, withoutlimitation, resorbable, remodelable, implantable, and/or biocompatiblecapacities.

Additional disclosures of submucosa technology may be found in thefollowing U.S. patent documents, each incorporated herein by referencethereto: U.S. Pat. No. 6,241,981 Composition and Method for RepairingNeurological Tissue; U.S. Pat. No. 6,176,880 Tissue Graft Construct forReplacement of Cartilaginous Structures; U.S. Pat. No. 6,096,347Myocardial Graft Constructs; U.S. Pat. No. 5,641,518 Method of RepairingBone Tissue; U.S. Pat. No. 5,445,833 Tendon or Ligament Graft forPromoting Autogenous Tissue Growth; U.S. Pat. No. 5,372,821 Graft forPromoting Autogenous Tissue Growth; U.S. Pat. No. 6,113,623 ProstheticDevice and Method for Eventration Repair; U.S. Pat. No. 5,743,917Prosthesis for the Repair of Soft Tissue Defects; U.S. Pat. No.5,725,577 Prosthesis for the Repair of Soft Tissue Defects; U.S. Pat.No. 6,391,538 Stabilization of Implantable Bioprosthetic Tissue; U.S.Pat. No. 6,334,872 Method for Treating Diseased or Damaged Organs;

U.S. Pat. No. 6,334,446 Medical Sling Procedures and Anchor InsertionMethods and Devices; U.S. Pat. No. 6,312,474 Resorbable ImplantMaterials; U.S. Pat. No. 6,171,344 Bladder Submucosa Seeded with Cellsfor Tissue Reconstruction; U.S. Pat. No. 5,733,337 Tissue Repair Fabric;U.S. Pat. No. 5,352,463 Tissue Graft for Surgical Reconstruction of aCollagenous Meniscus and Method Therefor; U.S. Pat. No. 5,275,826Fluidized Intestinal Submucosa and its Use as an Injectable TissueGraft; U.S. Pat. No. 6,485,723 Enhanced Submucosal Tissue GraftConstructs; U.S. Pat. No. 6,375,989 Submucosa Extracts; U.S. Pat. No.6,099,567 Stomach Submucosa Derived Tissue Graft; U.S. Pat. No.5,997,575 Perforated Submucosal Tissue Graft Constructs; U.S. Pat. No.5,968,096 Method of Repairing Perforated Submucosal Tissue GraftConstructs; U.S. Pat. No. 5,762,966 Tissue Graft and Method for UrinaryTract Urothelium Reconstruction and Replacement; U.S. Pat. No. 5,755,791Perforated Submucosal Tissue Graft Constructs; U.S. Pat. No. 5,554,389Urinary Bladder Submucosa Derived Tissue Graft; U.S. Pat. No. 5,516,533Fluidized Intestinal Submucosa and its Use as an Injectable TissueGraft; U.S. Pat. No. 4,956,178 Tissue Graft Composition; U.S. Pat. No.4,902,508 Tissue Graft Composition; and U.S. Pat. No. 5,711,969 LargeArea Submucosal Tissue Graft Constructs.

Referring now to FIG. 2, there is shown an illustrative surgicalconfiguration of mesh 10 in which mesh 10 is placed in effectiveproximal juxtaposition to an illustrative abdominal incision 12 duringan abdominal closure routine, according to another form of theinvention. As shown, mesh 10 has been applied by suitable surgical meansto close or otherwise facilitate and/or assist in the closure of theabdominal incision 12. As discussed below, the illustrated use of mesh10 is especially provided as preventative care to prevent, oppose, orcounter the occurrence or incidence of incisional hernias stemming fromherniation via incision 12.

In alternate forms, it should be considered that incision 12 is merelyrepresentative of any breach in the abdominal wall anatomy and is notlimited to incisional-type openings such as depicted in FIG. 2.Accordingly, the invention can be practiced with equal effectiveness toclose any breach in the abdominal wall, whether from an incision orotherwise from other causes.

In alternate forms, mesh 10 can be used to reinforce an existingconventional incisional suture or can serve as the entire and soleabdominal incision closure mechanism. In one advantage of the invention,the use of mesh 10 can be readily incorporated into the normal andconventional abdominal closure routine as a primary orsupplemental/secondary suturing or closure protocol. It should beapparent that the invention can be practiced in any surgical, medical oroperating application where an abdominal incision has been made orotherwise when abdominal closure is indicated. For example, theinvention can be practiced in surgical environments where abdominalclosure is indicated due to non-incisional breaches of the abdominalwall or anatomy. For example, as discussed further, the invention can beapplied to the repair of both incisional and non-incisional herniadefects.

Referring again to FIG. 2, incision 12 is shown with now-closed incisionline 14 made in an anatomical or physiological entity 16 (shown infragmented form), such as the abdominal wall. As shown, exemplarysutures 18 have been incorporated to surgically close and/or sealincision 12, in a manner known to those skilled in the art andparticularly in accordance with well known surgical routines andspecifications.

According to the invention, submucosa mesh 10 is disposed in overlyingcovering relationship to incision 12 or otherwise applied to incision 12in a manner that fosters or promotes integrity of the abdominal wallclosure, e.g., retention and stability of sutures 18. The extent of thecoverage of incision 12 afforded by the superimposition of mesh 10 maytake on any of various forms. For example, while it is preferred thatmesh 10 completely cover incision 12, partial coverage is also possible.

The installed, implanted, or working relationship of mesh 10 to incision12 is preferably characterized by a contacting relationship between thesubmucosal tissue of mesh 10 and at least the portion of the abdominalwall 16 at and around incision 12. Preferably, the entire side of mesh10 facing incision 12 (e.g., the application side) forms asurface-to-surface contacting relationship with the anatomical surfaceof the abdominal wall in direct opposition thereto. In this manner, thesubmucosal tissue of mesh 10 is absorbed or otherwise assimilated intothe physiological structure of the abdominal wall and becomes aneffective functional portion thereof.

It should be apparent that the construction and application of mesh 10to incision 12 is made with a view towards accomplishing or otherwisefacilitating, promoting, or fostering abdominal wall closure.Accordingly, to achieve this end, any conventional surgical proceduresand techniques known to those skilled in the art may be used toincorporate or otherwise deploy mesh 10 into the body at incision 12.

In alternate forms, a surgical procedure may be developed that deploysmesh 10 into the body at incision 12 as the primary suturing mechanism,namely, without the use of suture threads 18. Conventional surgicalmethods may be used to prepare incision 12 for singular closure by theuse of mesh 10.

Although a single mesh 10 is shown in FIG. 2, this depiction should notbe considered in limitation of the invention, as any arrangement of suchmeshes 10 may be employed. In one configuration, a series of individualmeshes 10 may be applied in succession to the incision area to form ahierarchical or layered arrangement exhibiting a sequence of reinforcingstructures. For example, working from the incision level outwards, asuccession of individual meshes 10 in increasing size may be applied inoverlying relationship to each other. To add further support, additionalmeshes 10 may also be used around the periphery of incision 12 inoverlapping relationship to the central mesh 10 that covers incision 12.

Any conventional means known to those skilled in the art may be used tounite, join, attach, or otherwise secure mesh 10 to abdominal wall 16.For example, as shown, mesh 10 is provided with an exemplary set ofperforations or holes 20 formed about its periphery to facilitatesuturing attachment to abdominal wall 16. Any number, arrangement andsize of perforations 20 may be used to facilitate the attachment of mesh10. Mesh 10 may also be attached by sutureless means.

It should also be apparent that the size and shape of mesh 10 is adaptedor otherwise accommodated to fit over incision 12 in a manner promotingabdominal wall closure. Incision 12 may also be closed or covered by aset of smaller individual submucosa mesh components that are arrangedserially along incision 12 in abutting or overlapping relationship, forexample. In this manner, if one mesh component fails or weakens, otherones of the mesh components may continue to provide independent supportto the abdominal incision closure.

One advantageous feature of deploying mesh 10 in the surgicalenvironment of FIG. 2 is that it prevents or at least resists orinhibits the occurrence or formation of an incisional hernia at theincision site 12. By applying mesh 10 to incision 12, a measure ofsupport is added to the abdominal closure that is not otherwiseavailable by the traditional use of normal sutures 18. Since thesubmucosa mesh 10 eventually biologically fuses to and/or is absorbedinto the surrounding anatomical area to which it is initially attached(e.g., the endogenous abdominal wall tissue structure), the integrityand strength of the as-absorbed mesh 10 will be commensurate with theintact abdominal wall, which in most cases will be more that sufficientto hold together, support and stabilize the abdominal wall closure.

In a typical incisional hernia, a precipitating event causes theabdominal wall closure to be breached. A scenario for an incisionalhernia typically exhibits some disruption to the stability of thesutures 18 that allows the abdominal incision to reopen. For example,the sutures 18 may be torn from their anchoring positions or a new tearin the abdominal wall may propagate from the ends of the originalincision. Whatever the cause, the integrity of the sutured closure iscompromised during an incisional hernia.

However, in the invention, the submucosa mesh construct is incorporatedinto the routine surgical abdominal wall closure in a manner that iseffective to at least mitigates the occurrence or recurrence of anincisional hernia. Unlike traditional scenarios where compromise of theclosure sutures can lead to incisional hernias, a breach in thesubmucosa mesh of the invention would also have to occur to initiate anincisional hernia. However, the comparatively higher strength andstability of the submucosa mesh relative to traditional suturessignificantly improves the integrity and durability of the abdominalclosure, particularly in regard to hernia incipience, onset, andincidence.

According to various functional characterizations, the submucosal mesh10 can be considered to support the abdominal closure and/or maintain,preserve, and sustain the abdominal closure.

Although the surgical technique shown in FIG. 2 is discussed in relationto abdominal closure protocols, it should be considered that theinvention can be practiced with incisional closure routines affectinganatomical entities other than the abdominal wall.

Referring now to FIG. 3, there is shown an illustrative surgicalconfiguration of mesh 10 deployed in the manner shown to repair a herniadefect (generally depicted at 30), according to another form of theinvention.

As shown, mesh 10 has been applied by suitable surgical means to repairhernia defect 30, e.g., to close or otherwise facilitate the closure ofthe hernia-type breach or opening. For comparison purposes, theuntreated hernia defect is depicted generally in exaggerated view bybreach or opening 30 (prior to the use of mesh 10), while the abdominalclosure line subsequent to practice of the invention is depictedgenerally at 32 to illustrate how hernia defect 30 is treated (e.g.,closed) by the use of mesh 10. As discussed below, the illustrated useof mesh 10 is especially suited as a repair mechanism to repairabdominal wall hernias.

It should be considered that the surgical abdominal closure techniqueillustrated by FIG. 3 can be employed in connection with any type ofhernia defect, regardless of cause and/or origin. For example, theillustrated surgical technique can be used in connection with incisionalor non-incisional hernias and with any type of hernia, including, butnot limited to, abdominal and inguinal.

The manner and aspects of applying submucosa mesh 10 to hernia defect 30to produce abdominal closure 32 is similar to the manner in which mesh10 is applied to incision 12 in FIG. 2. In all other respects, thesurgical technique illustrated by FIG. 3 is similar to conventionalprocedures known to those skilled in the art for surgically treating andaddressing hernia defects. For example, although not shown, sutures maybe used to initially close hernia defect 30, followed by deployment andimplantation of mesh 10. Optionally, the abdominal closure 32 may berealized without the use of such sutures, in which mesh 10 singularlyprovides the suturing support sufficient to accomplish repair or closureof the hernia defect.

Referring now to FIG. 4, there is shown a matrix or network 40 ofindividual discrete submucosa patch elements 42 arranged and adapted assuturing components to cooperatively provide a suture-type closure(depicted generally at 44), according to another form of the invention.

In one form, submucosa patch elements 42 are constituted as compact orsubcompact versions of the submucosa mesh 10 in FIG. 1. Accordingly, themanner, feature and aspects of making and forming patch 42 is similar tomesh 10, as discussed above. The arrangement of patch elements 42 may beused to define the suturing or closure mechanism in any surgicalapplication. For example, the patch elements 42 may be used as areplacement for conventional threaded sutures employed to close anincision, hernia defect, or other unwanted breach or opening.Additionally, patch elements 42 may be used in conjunction with anyanatomical site, including, but not limited to, abdominal wall closures.

In one advantageous feature, the patch elements 42 may be used incombination with mesh 10 (FIG. 1) to constitute an entirelysubmucosa-based or submucosa-derived construct assembly capable ofproviding the following functionalities: (i) suturing the abdominalopening with patch elements 42, and (ii) supporting the suturedabdominal closure with mesh 10. FIG. 5 illustrates an exemplaryconfiguration that employs such a combination.

In one form, the submucosa patch elements 42 may be consideredbioretention sutures, which preferably take the place of externalretention sutures currently in use. The advantage of such internalsubmucosa retention sutures is that these tissue components arereabsorbed into the host or carrier site which accepts patch elements 42(e.g., abdominal wall), and therefore do not have to be removed likeexternal sutures.

Additionally, internal bioretention sutures provide long-term strengthsince they remain fully intact and permanently resident within the body.The added strength is notably apparent and beneficial to fascialclosures.

Current retention sutures are very painful to the patient since they areexternal and therefore tend to pull on the abdominal wall. Additionally,external sutures tend to dig into the skin and thereby cause irritation,infection, and unsightly scars. However, the internal bioretentionsutures of the invention exhibit none of these problems. Furthermore, ascompared to external sutures that are eventually removed, the implantedinternal bioretention sutures provide continuous added strength,particularly to abdominal wall closures where elevated stresses andstrains can occur that weaken traditional sutured closures and make thearea vulnerable or susceptible to herniation.

According to another form of the invention, the submucosa construct canbe adapted for use as part of a surgical strategy to facilitate woundhealing or treatment, regeneration, support, reconstruction, andreplacement of anatomical structures, such as tissues and organs,without any loss or diminution in mechanical functionality, kinematiccapabilities, or other functional or biological properties.

For example, the submucosa constructs discussed herein can be adapted inany suitable manner to form a scaffold-type article that serves as aplatform for substitution in the anatomy. For example, the submucosaconstruct can replace in whole or in part an organ or other structure ofthe body. The replacement strategy, for example, can be devised toreplace damaged or diseased structures. The construct can also beadapted to facilitate regeneration and synthesis with the surroundinganatomical environment.

Suitable means known to those skilled in the art can be employed tofashion the replacement or substitute submucosa construct, such as inaccordance with the functional and structural specifications of thetarget environment or destination in the body. For example, theconstruct can be formed entirely of submucosa, or combined with anynumber of diverse elements, such as synthetic and natural materials toenhance the regrowth, synthesis, and physiological/biological acceptanceof the introduced construct.

By way of background, in regard to the acquisition and preparation ofthe submucosal tissue constructs/articles, the invention as discussedherein is directed to a tissue graft composition (e.g., mesh 10)comprising primarily the tunica submucosa of a segment of smallintestine of a warm-blooded vertebrate. The tunica submucosa isdelaminated from the tunica muscularis and at least the luminal portionof the tunica mucosa of the section of small intestine. The presenttissue graft composition exhibits excellent functional characteristicsin various graft applications, including, but not limited to,autografts, allografts, heterografts, homografts, and xenografts.

The tissue graft composition exhibits multiple physical and biologicalcharacteristics that renders it particularly adapted for tissue graftapplications.

In one form, the tissue graft material comprises submucosa tissue andbasilar mucosa tissue delaminated from a segment of the small intestine,more preferably the jejunum, a division of the small intestine extendingbetween the duodenum and the ileum. The small intestine, prior to itsmanipulation (delamination) to yield graft material in accordance withthis invention, is made up of a number of discrete tissue layersdefining the intestinal wall. The outermost tissue layer is themesenteric tissues. The next successive layers are the tunica serosa andthe tunica muscularis, respectively. The next layer, the tunicasubmucosa, is a dense, irregular collagenous connective tissue oftenharboring numerous mast cells.

The next set of tissue layers collectively represent the so-calledtunica mucosa. The first layer of the tunica mucosa is a layer of smoothmuscle cells known as the lamina muscularis mucosa. The next layer, thestratum compactum, consists of acellular collagen and elastin fibers.The next layer consists of the lamina epithelialis mucosa and its laminapropria, which together and arranged in villous processes, a series offinger-like outgrowths of the mucous membrane.

Following the below-detailed manipulation of the intestinal tissuesegment to prepare the graft material of this invention, histologicexamination reveals that the lamina epithelialis mucosa and its laminapropria have been removed, as have the tunica muscularis and the tunicaserosa. In one form, the graft material of this invention thus comprisesthe tunica submucosa, along with basilar portions of the tunica mucosa,particularly the lamina muscularis mucosa and the stratum compactum.Those layers collectively are referred to as the Small IntestineSubmucosa (“SIS”).

An SIS autograft in accordance this invention can be prepared, forexample, by first resecting a segment of autogeneous proximal jejunumfollowing a midline laparotomy incision. The resected segment of jejunumis then wrapped in surgical sponges which have been soaked inphysiologic saline. Upon completion of the intestinal anastomosis, theexcised intestinal segment is prepared in accordance with thehereinafter described method for use as a tissue graft material.Similarly, allografts are prepared from intestinal tissue removed fromorgan/tissue donors of the same species. Heterografts can be prepared,for example, from feline, porcine, or bovine intestinal tissue retrievedfrom euthanized animals at slaughterhouse operations. For example, pigintestine can be harvested. To date, minimal morphological differenceshave been found in intestinal tissues from different species.

In one exemplary protocol, the tissue graft material of this inventionis prepared by abrading intestinal tissue to remove the outer layersincluding both the tunica serosa and the tunica muscularis and the innerlayers including at least the luminal portion of the tunica mucosa.Under conditions of mild abrasion the tunica mucosa is delaminatedbetween the stratum compactum and the lamina propria. More particularly,following removal of any mesenteric tissues from the intestinal segmentutilizing, for example, Adson-Brown forceps and Metzenbaum scissors, thetunica serosa and the tunica muscularis (the outer tissue layers) aredelaminated from the intestinal segment by abrasion using a longitudinalwiping motion with a scalpel handle and moistened gauze.

Following eversion of the intestinal segment, the luminal portion of thetunica mucosa is delaminated from the underlying tissue using the samewiping motion. Care is taken to prevent perforation of the submucosa.Optionally, the intestinal segment may be everted first, then strippedof the luminal layers, then reinserted to its original orientation forremoval of the tunica serosa and the tunica muscularis. The graftmaterial is a whitish, translucent tube of tissue approximately 0.1 mmthick (although other suitable thicknesses are possible), typicallyconsisting of the tunica submucosa with the attached lamina muscularismucosa and stratum compactum. For graft preparation, for example, theprepared graft may be everted to its original orientation so that thestratum compactum serves as the luminal surface of the graft.

The prepared graft material is typically rinsed with saline and placedin a 10% neomycin sulfate solution for approximately 20 minutes, afterwhich time the graft material is ready for use. The grafts are appliedusing routine surgical procedures commonly employed for tissue graftapplications. For use in tissue graft applications, the tubular graftmaterial can be cut longitudinally and rolled out to form a “patch” oftissue.

Indeed, the entire tissue delamination procedure described above can becarried out on “patches” of intestinal tissue prepared by cutting theintestinal segment longitudinally and “unrolling” it to form a pre-graftpatch. The prepared graft tissue patches can be utilized, for example,as a graft material or for repair of other body tissue defects lendingthemselves to surgical application of a tissue graft patch having thephysical and functional characteristics of the present graftcomposition.

Consistent with the objects of this invention, the SIS compositionpossesses mechanical properties highly desirable for tissue graftmaterials, including low porosity index, high compliance, and a highburst pressure point. As for porosity, one skilled in the art willappreciate that tissue graft material must be of low enough porosity toprevent intraoperative hemorrhage and yet of high enough porosity toallow extension of a newly-developed vasa vasorum through the graftmaterial to nourish the neointima and luminal surface.

Regarding graft compliance, there has been described in the art theexistence of a direct relationship between compliance and patency.Ideally the graft material herein should be at least as compliant as thetissue it replaces.

In alternate forms, the formation of tissue graft constructs hereincomprises large area sheets of submucosal tissue. The fabricationcomprises the steps of fusing multiple strips of submucosal tissue toform unitary heterolaminar, and optionally multi-ply sheets ofsubmucosal tissue.

Furthermore, in other forms, the submucosal tissue suitable for use inthe formation of the present graft constructs comprises naturallyassociated extracellular matrix proteins, glycoproteins and otherfactors. One source of submucosal tissue is the intestinal tissue of awarm-blooded vertebrate. Small intestinal tissue is a preferred sourceof submucosal tissue for use in this invention.

Suitable intestinal submucosal tissue typically comprises the tunicasubmucosa delaminated from both the tunica muscularis and at least theluminal portion of the tunica mucosa. In one form, the intestinalsubmucosal tissue comprises the tunica submucosa and basilar portions ofthe tunica mucosa including the lamina muscularis mucosa and the stratumcompactum which layers are known to vary in thickness and in definitiondependent on the source vertebrate species.

Generally, the preparation of submucosal tissue for use in accordancewith this invention involves a segment of vertebrate intestine, such asharvested from porcine, ovine or bovine species, but not excluding otherspecies, that is subjected to abrasion using a longitudinal wipingmotion to remove the outer layers, comprising smooth muscle tissues, andthe innermost layer, i.e., the luminal portion of the tunica mucosa. Asimilar procedure can be used to prepare submucosa tissue from urinarybladder. The submucosal tissue is rinsed with saline and optionallysterilized; it can be stored in a hydrated or dehydrated state.Lyophilized or air dried submucosa tissue can be rehydrated and used inaccordance with this invention without significant loss of its biotropicand mechanical properties.

In another form, large area compliant sheets of submucosal tissue areformed from multiple partially overlapped strips of submucosal tissue.The dimensions of the individual strips of submucosal tissue used is notcritical and the term “strip of submucosal tissue” is defined herein toinclude submucosal tissue from one or more vertebrate sources or organsin a wide variety of sizes and shapes. The amount of tissue overlapbetween the adjacent strips of submucosal tissue can be varied based onthe intended use and the desired properties of the large area graftconstruct, provided that at least a portion of each strip of submucosaltissue overlaps with a portion of another strip of submucosal tissue.The strips of submucosal tissue are fused to one another along theoverlapped portions, producing a compliant unitary heterolaminar sheetof submucosal tissue. The term “heterolaminar” as used herein refers tothe variability in the number of layers of submucosa superimposed at(and fused) at different points on the unitary graft construct. Theheterolaminar structure of the present graft constructs, especially inmulti-ply constructs, provides enhanced mechanical strength.

Submucosal tissue typically has an abluminal and a luminal surface. Theluminal surface is the submucosal surface facing the lumen of the organsource and typically adjacent to an inner mucosa layer in vivo whereasthe abluminal surface is the submucosal surface facing away from thelumen of the organ source and typically in contact with smooth muscletissue in vivo. The multiple strips of submucosal tissue can beoverlapped with the abluminal surface contacting the luminal surface,the luminal surface contacting the luminal surface or with the abluminalsurface contacting the abluminal surface of an adjacent strip ofsubmucosal tissue. All of these combinations of overlapping strips ofsubmucosal tissue from some or different vertebrate or organ sourceswill produce a large area sheet of submucosal tissue.

Notwithstanding the above, it should be apparent that the submucosaltissue composition disclosed herein can be acquired, prepared, derived,manufactured, processed, treated, conditioned, and otherwise suppliedaccording to other means and processes known to those skilled in theart. Accordingly, the above description of the manufacture of thesubmucosal tissue is illustrative and should not be considered inlimitation of the invention.

While this invention has been described as having a preferred design,the present invention can be further modified within the spirit andscope of this disclosure. This application is therefore intended tocover any variations, uses, or adaptations of the invention using itsgeneral principles. Further, this application is intended to cover suchdepartures from the present disclosure as come within known or customarypractice in the art to which this invention pertains and which fallwithin the limits of the appended claims.

1. A method of treating or promoting the integrity of an incisionalabdominal wall closure, said method comprising the steps of forming anincisional abdominal wall closure then contacting at least part of theabdominal wall closure or at least part of the abdominal wall proximalto said closure with a composition comprising submucosal tissue toreduce the potential for an incisional hernia.
 2. The method as recitedin claim 1, wherein the submucosal tissue includes submucosal tissue ofa warm-blooded vertebrate.
 3. (canceled)
 4. The method as recited inclaim 1, wherein the submucosal tissue includes intestinal tissuedelaminated from both the tunica muscularis and at least the luminalportion of the tunica mucosa of the intestinal tissue.
 5. A method ofresisting the occurrence of an incisional hernia at an incisionalabdominal wall closure, said method comprising contacting at least partof the incisional abdominal wall closure or at least part of theincisional abdominal wall proximal to the closure with a compositioncomprising submucosal tissue.
 6. A method of treating an incision, saidmethod comprising suturing the incision with at least one element eachoverlying and/or engaging at least part of the incision, each elementincluding a composition comprising submucosal tissue to prevent theoccurrence of an incisional hernia.
 7. A tissue graft construct suitablefor use in supporting or maintaining an abdominal closure by surgicalapplication thereto, said construct comprising submucosal tissue thatincludes intestinal tissue delaminated from both the tunica muscularisand at least the luminal portion of the tunica mucosa of the intestinaltissue.
 8. A tissue graft construct suitable for use as a suture, saidconstruct comprising at least one mesh of submucosal tissue adapted forsuturing that includes intestinal tissue delaminated from both thetunica muscularis and at least the luminal portion of the tunica mucosaof the intestinal tissue.
 9. A method of promoting the maintenance of anabdominal wall closure, said method comprising applying an articlecomprising submucosal tissue to the abdominal wall closure and/or to theabdominal wall proximal to the closure said submucolsal tissue thatincludes intestinal tissue delaminated from both the tunica muscularisand at least the luminal portion of the tunica mucosa of the intestinaltissue.
 10. The method as recited in claim 9, wherein the articledefining a construct that is formed and adapted to facilitate avoidanceof an incisional hernia at the abdominal wall closure.
 11. The method asrecited in claim 9, wherein the applying step includes one of overlyingor engaging at least part of the abdominal wall closure with thearticle.
 12. The method as recited in claim 9, wherein the abdominalwall closure surgically addresses an incision.
 13. An article ofmanufacture adapted for use as a suture, said article comprising atleast one suture component comprising a composition of submucosaltissue.